(a) Field of the Invention
This invention relates to provide novel analogs of nonreducing monosaccharide subunit of lipid A and stereoisomers thereof. These novel compounds have been synthesized by the present inventors in their course of investigating an effective sugar moiety, which is expected to generate a greater part of the biological and immunological activities which are exhibited by natural lipid A.
(b) Description of the Prior Art
Lipo-polysaccharides are found in the cell-wall of some kinds of gram-negative bacilli as a main component of endotoxin. They exhibit various kinds of biological and immunological activities such as an anti-tumor activity. Lipid A is a lipoid component of lipo-polysaccharides. It is known that the biological and immunological activities is lipo-polysaccharides mostly depend on the lipid A component.
In an attempt to elucidate the chemical structure of lipid A, and to synthesize analogs of sugar moieties of lipid A which exhibit as many biological and immunological properties of natural lipid A as possible, compounds of the following formula have been described by Galanos and Ludritz et al. in 1977 [cf. Int. Rev. Biochem. 14: 239 (1977) and Naturwissensch. 65: 578 (1987)] ##STR2## wherein R represents a hydrogen atom or the residue of straight chain aliphatic acid having 12 to 16 carbon atoms, especially myristic acid, that is tetradecanoic acid, represented by a chemical formula of CH.sub.3 (CH.sub.2).sub.12 COOH.
The compounds of the above structure are characterized by two glucosamine groups which are linked together at their 1- and 6'-positions and the amino groups are located at the 2- and 2'-positions and the hydroxy groups are located at the 3- and 3'-positions of the glucosamine groups. Moreover, 3-hydroxy-myristic acid residue are attached by an amide or an ester linkage and the phosphoric acid groups are linked to the 1- and 4'-positions, respectively of the glucosamine groups. The compounds thus simultaneously have both hydrophilic and lipophilic substituents on the glucosamine groups.
In the above chemical formula, the left-handed glucosamine group is called the nonreducing subunit.
On the assumption that it is the nonreducing subunit where the biological and immunological activities of lipid A are mainly concentrated, the inventors have carried out extensive research to synthsize analogs of the nonreducing sugar subunit of lipid A and the thus synthesized products have successively been subjected to a primary biological experiment for screening out, then have achieved the present invention.